Microcystin-LR acute exposure increases AChE activity via transcriptional ache activation in zebrafish (Danio rerio) brain

Microcystins (MCs) constitute a family of cyanobacterial toxins, with more than 80 variants. These toxins are able to induce hepatotoxicity in several organisms mainly through the inhibition of protein phosphatases PP1 and PP2A and oxidative stress generation. Since recent evidence shows that MCs can either accumulate in brain or alter behavior patterns of fish species, in this study we tested the in vitro and in vivo effects of MC-LR at different concentrations on acetylcholinesterase (AChE) activity in zebrafish brain. In vivo studies showed that 100 μg/L MC-LR led to a significant increase in the AChE activity (27%) when zebrafish were exposed to the toxin dissolved in water, but did not cause any significant changes when injected intraperitoneally. In addition, semiquantitative RT-PCR analysis demonstrated that 100 μg/L MC-LR exposure also increased ache mRNA levels in zebrafish brain. The in vitro assays did not reveal any significant changes in AChE activity. These findings provide the first evidence that brain AChE is another potential target for MCs and suggest that the observed increases in AChE enzymatic activity and in ache transcript levels after MC-LR exposure depend, at least partially, on branchial uptake or ingestion.